Morton M F, Harper E A, Tavares I A, Shankley N P
Academic Department of Surgery, GKT Schools of Medicine and Dentistry, King's College, London SE5 9NU.
Br J Pharmacol. 2003 Sep;140(1):218-24. doi: 10.1038/sj.bjp.0705423. Epub 2003 Aug 4.
(1) The alternatively spliced, short and long cholecystokinin receptors (CCK2S and CCK2L) were expressed in NIH3T3 cells, and compared using radioligand-binding assays with identical buffer and incubation conditions. (2) As judged by a saturation analysis, the selective CCK2-receptor antagonist radioligand [3H]-JB93182 did not discriminate between the CCK2S or CCK2L receptors. (3) A global analysis of competition studies, using a range of structurally diverse, CCK-receptor selective ligands, provided further evidence that these receptor subtypes were pharmacologically indistinguishable. However, when analysed individually a number of small, yet significant differences were observed with some of the compounds. (4) These data are consistent with previous study that suggested a possible pharmacological difference between these isoforms, at least in terms of the CCK2-receptor antagonist, L-365,260. However, it would appear that the pharmacological profile of these compounds is not consistent with their affinity at the putative G1/G2 receptors previously described by Harper et al.
(1) 可变剪接产生的短型和长型胆囊收缩素受体（CCK2S和CCK2L）在NIH3T3细胞中表达，并在相同缓冲液和孵育条件下使用放射性配体结合试验进行比较。(2) 通过饱和分析判断，选择性CCK2受体拮抗剂放射性配体[3H]-JB93182无法区分CCK2S或CCK2L受体。(3) 使用一系列结构多样的CCK受体选择性配体对竞争研究进行整体分析，进一步证明这些受体亚型在药理学上无法区分。然而，单独分析时，观察到一些化合物存在一些虽小但显著的差异。(4) 这些数据与先前的研究一致，该研究表明这些异构体之间可能存在药理学差异，至少就CCK2受体拮抗剂L-365,260而言。然而，这些化合物的药理学特征似乎与其对Harper等人先前描述的假定G1/G2受体的亲和力不一致。
